Plasmapheresis therapy was not successful in four patients with systemic lupus erythematosus. Each of the patients had a flare within four months of instituting therapy requiring vigorous conventional therapy to reinduce remission in these patients. Before it can be stated unequivocally that plasmapheresis is effective in systemic lupus erythematosus, large scale controlled studies need to be performed. Immune complex size was found to be important in the different manifestations of disease in patients with systemic lupus. Patients with membranous glomerulonephritis had exclusively large complexes (greater than 19S) while those with cerebritis had exclusively small complexes (less than or equal to 7S). Patients with diffuse proliferative and non-renal lupus had both large and small complexes. Specificity of lymphocytotoxic antibodies in most patients with systemic lupus and some of their relatives are directed against determinants present on major histocompatability gene products found on lymphocyte surfaces. This was suggestive that lymphocytotoxic antibodies in relatives represent a defect in immune regulation which allows expression of existing autoimmune potentials rather than immunization with a single "lupus" antigen.